We have developed a system to study the changes in gene expression in CD4+ T lymphocytes that occur during human immunodeficiency virus (HIV) infection. Using mRNA differential display and the related arbitrarily-primed polymerase chain reaction (PCR) of mRNA, we identified 41 "bands" which are apparently differentially expressed between primary human peripheral blood CD4+ cells and those same cells exposed to primary HIV-1 virions for 2 to 5 hours. We hoped to identify cellular genes whose expression is upregulated by simple encounter with virions. We reasoned that these genes turned on early upon encounter with virus could be important not only for cells which eventually become productively-infected, but also for those cells rendered dysfunctional without producing progeny virus. Since most virions are defective, perhaps cells which encounter quasispecies are dysregulated and account for some of the immunopatholology of HIV disease. Putatively differentially expressed bands were confirmed by reverse transcription (RT)-PCR. Three genes verified as dysregulated were identified. Band 5 is the newly-described intracellular proteinase inhibitor CAP3. The product of this gene closely resembles a member of the ICE [interleukin (IL)-1beta converting enzyme] family of proteinase inhibitors. Band 15 is identical to an uncharacterized EST which shares some homology with 2 genes of the ets family of transcription factors. Band 8 is novel. Ongoing work is aimed at ascertaining the roles of these genes in HIV pathogenesis/immune dysregulation. These studies may enable us to delineate, at the molecular level, certain of the mechanisms of HIV-induced immune dysfunction.